The major goal of the proposed study is to investigate the structural mechanisms linking depression and dementia. Specifically we will examine 1) whether demented individuals with a significant history of depression have a higher prevalence of white matter hypodensities (WMH), cerebral atrophy, basal gangliathalamic lesions, or cerebral infarct on computed tomographic (CT) scans, compared to individuals with dementia and no significant history of depression, 2) whether these differences between individuals with and individuals without depression vary based upon the timing of the onset of depression, and 3) whether depression alone affects the course of dementia. The proposed study will use a population-based sample of data drawn from individuals who participated in the Study of Dementia in Swedish Twins, which includes all twins from the Swedish Twin Registry who were at least age 65 and alive during the screening phase. Our sample (N=620) will consist of all twins diagnosed with dementia, a subset of whom (N=280) had a CT scan performed as part of the clinical phase of dementia assessment. CT scans will be assessed using visual rating scales for the extent or density of WMH throughout the periventricular and subcortical white matter, the sulcal and ventricular enlargement as a measure of overall atrophy, as well as for the presence of basal ganglia-thalamic lesions and number of infarcts. Analyses will include ordered logit analysis, multiple analysis of covariance, and Cox proportional hazard models. Age, gender, education, and vascular disease will all be examined as potential confounders. Analyses will be conducted for total dementia and for Alzheimer's disease or vascular dementia alone. The import of this research project is underscored in the recommendations provided by the proceedings of the 2003 NIMH conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" (Steffens et al., 2006), which state that "[additional studies are needed to followup on the implications of these [underlying neurobiological disturbances] to understand the mechanisms linking depression and dementia" (pp. 134-135). For older adults with dementia and depression, there are important public health implications to identifying whether depression increases the structural changes in the brain commonly associated with dementia, or if it exacerbates the cognitive symptoms of dementia, without producing any additional structural changes. Since the clinical reality is that nearly one-quarter of older adults experience significant depression and approximately the same proportion experience cognitive impairment, this truly is a "current research imperative" (Steffens et al., 2006, p. 130).